Heart failure (HF) is the leading cause of hospitalization among elderly people in the US with an annual incidence rate of 550,000 cases. Despite advances in medical and surgical treatment, mortality after the onset of HF remains high. Given the growing number of older adults in the US, it is imperative to prevent the occurrence of this condition. This calls for innovative research that could provide cost-effective intervention tools to improve the management and prevention of HF. To this end, dietary intake of long-chain omega-3 (n-3) fatty acids has been shown to lower the risk of myocardial infarction and hypertension - two major risk factors for HF. In addition, n-3 fatty acids have been shown to attenuate ventricular remodeling and dysfunction induced by pressure overload in animal models. Current epidemiologic evidence to support such beneficial effect of n-3 fatty acids on HF comes from the Cardiovascular Health Study in which self-reported fish consumption was associated with a lower risk of HF in older adults. However, no data are available on the effects of n-3 fatty acids on HF subtypes (systolic vs. diastolic HF) or HF etiology (for example: ischemic vs. non-ischemic HF). Likewise, it is not clear whether other fatty acids such as trans fatty acids (known to increase the risk of coronary heart disease) or short-chain fatty acids found abundantly in vegetables (and cheaper than fish) could prevent the occurrence of HF. In the absence of a study examining the relation between n-3 fatty acid supplements and risk of HF, it is unclear whether n-3 in fish, other nutrients in fish, or lifestyle factors associated with fish consumption were responsible for the observed effects of fish intake on HF risk. More importantly, bias inherent to self-reported data might lead to erroneous conclusions. The current application will not suffer from such limitations as it will examine the association between plasma phospholipid n-3 fatty acids (both long-chain and short- chain) and trans fatty acids and HF among US male physicians using a reproducible method to measure fatty acid intake. Furthermore, we will assess the relation between plasma phospholipid n-3 fatty acids and HF subtypes as well as HF etiology. Findings of this study will a) help determine whether n-3 fatty acids are important in the development of HF, b) inform the scientific community in designing potential future clinical trials of diet and/or supplements on the risk of HF, and c) help identify dietary factors that could be use along with other measures to prevent HF. Results on trans fats may provide additional evidence to support legislative action on the usage of trans fatty acids. The fact that the costs for subject recruitment, sample collection, information on key covariates and confounders, etc, have been covered by the parent study makes this application highly cost-efficient. PUBLIC HEALTH RELEVANCE: As the leading cause of hospitalization among elderly people in the US, heart failure is still a major public health issue. Little is known about the role of dietary fatty acids on the risk of heart failure. If the current project identifies dietary factors that influence the risk of heart failure, then such information could help reshape dietary guidelines as a major component of prevention strategies designed to lower the risk of heart failure in the population.